Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial.
Kunzmann Volker,Siveke Jens T,Algül Hana,Goekkurt Eray,Siegler Gabriele,Martens Uwe,Waldschmidt Dirk,Pelzer Uwe,Fuchs Martin,Kullmann Frank,Boeck Stefan,Ettrich Thomas J,Held Swantje,Keller Ralph,Klein Ingo,Germer Christoph-Thomas,Stein Hubert,Friess Helmut,Bahra Marcus,Jakobs Ralf,Hartlapp Ingo,Heinemann Volker,
The lancet. Gastroenterology & hepatology
BACKGROUND:The optimal preoperative treatment for locally advanced pancreatic cancer is unknown. We aimed to compare the efficacy and safety of nab-paclitaxel plus gemcitabine with nab-paclitaxel plus gemcitabine followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) as multidrug induction chemotherapy regimens in locally advanced pancreatic cancer. METHODS:In this open-label, multicentre, randomised phase 2 study, done at 28 centres in Germany, eligible patients were adults (aged 18-75 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically or cytologically confirmed, treatment-naive locally advanced pancreatic adenocarcinoma, as determined by local multidisciplinary team review. After two cycles of nab-paclitaxel 125 mg/m plus gemcitabine 1000 mg/m (administered intravenously on days 1, 8, and 15 of each 28-day cycle), patients without progressive disease or unacceptable adverse events were randomly assigned (1:1) to receive either two additional cycles of nab-paclitaxel plus gemcitabine (nab-paclitaxel plus gemcitabine group) or four cycles of sequential FOLFIRINOX (oxaliplatin 85 mg/m, leucovorin 400 mg/m, irinotecan 180 mg/m, fluorouracil 400 mg/m by intravenous bolus followed by a continuous intravenous infusion of 2400 mg/m for 46 h on day 1 of each 14-day cycle; sequential FOLFIRINOX group). Randomisation was done by the clinical research organisation on request of the trial centre using a permuted block design (block size 2 and 4). Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was surgical conversion rate (complete macroscopic tumour resection) in the randomised population by intention-to-treat analysis, which was assessed by surgical exploration in all patients with at least stable disease after completion of induction chemotherapy. This trial is registered with ClinicalTrials.gov, NCT02125136. FINDINGS:Between Nov 18, 2014, and April 27, 2018, 168 patients were registered and 130 were randomly assigned to either the nab-paclitaxel plus gemcitabine group (64 patients) or the sequential FOLFIRINOX group (66 patients). Surgical exploration after completed induction chemotherapy was done in 40 (63%) of 64 patients in the nab-paclitaxel plus gemcitabine group and 42 (64%) of 66 patients in the sequential FOLFIRINOX group. 23 patients in the nab-paclitaxel plus gemcitabine group and 29 in the sequential FOLFIRINOX group had complete macroscopic tumour resection, yielding a surgical conversion rate of 35·9% (95% CI 24·3-48·9) in the nab-paclitaxel plus gemcitabine group and 43·9% (31·7-56·7) in the sequential FOLFIRINOX group (odds ratio 0·72 [95% CI 0·35-1·45]; p=0·38). At a median follow-up of 24·9 months (95% CI 21·8-27·6), median overall survival was 18·5 months (95% CI 14·4-21·5) in the nab-paclitaxel plus gemcitabine group and 20·7 months (13·9-28·7) in the sequential FOLFIRINOX group (hazard ratio 0·86 [95% CI 0·55-1·36]; p=0·53). All other secondary efficacy endpoints, such as investigator-assessed progression-free survival, radiographic response rate, CA 19-9 response rate, and R0 resection rate, were not significantly different between the two treatment groups except for improved histopathological downstaging in evaluable resection specimens from the sequential FOLFIRINOX group (ypT1/2 stage: 20 [69%] of 29 patients in the sequential FOLFIRINOX group vs four [17%] of 23 patients in the nab-paclitaxel plus gemcitabine group, p=0·0003; ypN0 stage: 15 [52%] of 29 patients in the sequential FOLFIRINOX group vs four [17%] of 23 patients in the nab-paclitaxel plus gemcitabine group, p=0·02). Grade 3 or higher treatment-emergent adverse events during induction chemotherapy occurred in 35 (55%) of 64 patients in nab-paclitaxel plus gemcitabine group and in 35 (53%) of 66 patients in the sequential FOLFIRINOX group. The most common of which were neutropenia (18 [28%] in nab-paclitaxel plus gemcitabine group, 16 [24%] in the sequential FOLFIRINOX group), nausea and vomiting (two [3%] in nab-paclitaxel plus gemcitabine group, eight [12%] in the sequential FOLFIRINOX group), and bile duct obstruction with cholangitis (six [9%] in nab-paclitaxel plus gemcitabine group, seven [11%] in the sequential FOLFIRINOX group). No deaths were caused by treatment-related adverse events during the induction chemotherapy phase. INTERPRETATION:Our findings suggest that nab-paclitaxel plus gemcitabine is similarly active and safe as nab-paclitaxel plus gemcitabine followed by FOLFIRINOX as multidrug induction chemotherapy regimens for locally advanced pancreatic cancer. Although conversion to resectability was achieved in about a third of patients, additional evidence is required to determine whether this translates into improved overall survival. FUNDING:Celgene.
10.1016/S2468-1253(20)30330-7
Strategy for treatment of stage IV human epidermal growth factor 2-positive gastric cancer: a case report.
Sakaguchi Masazumi,Shimoike Norihiro,Akagawa Shin,Kanaya Seiichiro
Journal of medical case reports
BACKGROUND:The prognosis of stage IV gastric cancer and human epidermal growth factor 2 (HER2)-positive gastric cancer is poor, although new drugs and regimens have been developed. We report a case of a patient with stage IV HER2-positive gastric cancer treated successfully by conversion therapy and trastuzumab. CASE PRESENTATION:The patient was a 73-year-old Japanese man diagnosed as L, type 3, circ, T4aNxCy1P1M1, stage IV (the Japanese classification of gastric carcinoma). The patient was treated with docetaxel, cisplatin, and TS-1 (DCS regimen). After two courses of the regimen, peritoneal dissemination disappeared, and peritoneal lavage cytology revealed no tumor cells in the abdominal cavity. Subsequently, he underwent laparoscopic distal gastrectomy with D1+. Pathological findings were ypT2(MP), ypN2(3/15), ypP0, ypCY0, M0, ypstage II. He received TS-1 as an adjuvant chemotherapy, but he had peritoneal recurrence. The original gastric cancer was HER2-positive. We therefore treated him with TS-1 with trastuzumab. This regimen was quite effective and achieved a complete response. After complete response, we switched the patient to trastuzumab monotherapy. He had no evidence of recurrence for 6 years, 3 months after surgery. CONCLUSION:DCS regimen, R0 resection, and adjuvant chemotherapy with trastuzumab can be a powerful strategy for stage IV HER2-positive gastric cancer.
10.1186/s13256-019-2001-3
Efficacy of Conversion Surgery Following Apatinib Plus Paclitaxel/S1 for Advanced Gastric Cancer With Unresectable Factors: A Multicenter, Single-Arm, Phase II Trial.
Xu Zhiyuan,Hu Can,Yu Jianfa,Du Yian,Hu Ping,Yu Guofa,Hu Conggang,Zhang Yu,Mao Wei,Chen Shanqi,Cheng Xiangdong
Frontiers in pharmacology
Conversion therapy (surgical resection after chemotherapy) is a promising option for unresectable gastric cancer (GC) patients. Addition of anti-angiogenesis drug improves response to chemotherapy. Hence, this study explored the feasibility and efficacy of preoperative paclitaxel (PTX)/S1 chemotherapy combined with apatinib for unresectable GC. Thirty-one eligible patients with a single unresectable factor were enrolled in this multi-center, single-arm trial. Apatinib (500 mg qd) was administered continuously, while PTX (130 mg/m) on day 1 and S1 (80 mg/m) on day 1-14 were given every 3 weeks. The treatment was given for three cycles preoperatively, but the last cycle did not include apatinib. The primary objective measurements included R0 resection rate, objective response rate (ORR) and morbidity of preoperative treatment. Among the 31 patients, 30 patients were evaluable for tumor response, the ORR to preoperative treatment was 73.3%. Eighteen of 30 patients underwent surgery, and R0 resection was achieved in 17 patients. The patients who underwent the conversion surgery had a superior OS compared with those who did not (3 years OS: 52.9 vs 8.3%, = 0.001). The surgery was operated after apatinib had stopped for a median duration of 4 weeks. Neither anastomotic leakage nor wound healing complications was observed. No increased bleeding event was observed compared with historical data. During preoperative treatment, grade 3 or 4 toxicities were experienced by 58.1% of the patients. Chemotherapy in combination with apatinib demonstrated higher rates of conversion and R0 resection and a superior survival benefit in initial unresectable GC. It is safe and reasonable to suspend apatinib for 4 weeks before the gastrectomy.
10.3389/fphar.2021.642511
[Effective S-1 plus Oxaliplatin(SOX)Therapy in Two Cases of Advanced Gastric Cancer That Was Difficult to Resect and R0 Surgery Could Be Performed].
Matsumoto Keita,Goto Ayana,Tajirika Toshihiro,Tochii Koya,Kimura Masaki,Hanatate Fumika,Sekino Takafumi,Matsunami Hidetoshi
Gan to kagaku ryoho. Cancer & chemotherapy
Case 1: A 59-year-old man was diagnosed with type 3 gastric cancer cStage Ⅲ(MU, Gre, tub2>por, cT4aN2M0)induced by gastric perforation. The first surgery involving resection of the lesser curvature of stomach lymph node was judged to be difficult, and eventually exploratory laparotomy was performed. He received 3 courses of chemotherapy using S-1 plus oxaliplatin(SOX)(S-1 120mg/m2/day, day 1-14, oxaliplatin 100 mg/m2, day 1, followed by 7 days of rest). He subsequently underwent curative laparotomy gastrectomy plus D2(-No. 10)lymph node dissection, and Roux-en-Y reconstruction. Histological type was judged to be Grade 3. Case 2: A 69-year-old man was diagnosed with type 2 esophageal gastric junctional cancer,(GE, Less, tub2, cT4aN3M1[LYM])of cStage Ⅳ. He received 6 courses of chemotherapy using trastuzu- mab plus S-1 plus oxaliplatin(HER plus SOX)(trastuzumab 8mg/kg[2nd course 6mg/kg], day 1, S-1 120mg/m2/day, day 1-14, oxaliplatin 100mg/m2[5th course 80 mg/m2], on day 1, followed by 7 days of rest). He subsequently underwent laparotomy of the lower esophageal total gastrectomy plus D2(-No. 10, +No. 16, No. 110)lymph node dissection, and Roux-en-Y reconstruction as conversion surgery. Histological type was Grade 3. Both were impressive cases suggesting the usefulness of SOX therapy as a multidisciplinary treatment strategy for advanced gastric cancer.
Conversion therapy for advanced gastric cancer with trastuzumab combined with chemotherapy: A case report.
Xiao Shuo-Meng,Xu Rui,Tang Xiao-Li,Ding Zhi,Li Ji-Man,Zhou Xiang
Oncology letters
Gastric cancer is a common cancer of the gastrointestinal tract and the second most prevalent cause of cancer-associated mortality globally. Gastric cancer-associated mortality is increased in China compared with that in other countries. Key contributors to the poor prognosis of gastric cancer include late clinical presentation and genetic heterogeneity. Treatment based on the subtype of gastric cancer is important for effective therapy. The overexpression of the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene and protein is associated with gastric cancer in humans. Chemotherapy and targeted therapy may control tumor growth and recurrence, which is an important function of conversion surgery. The present study reported a patient diagnosed with gastric cancer with multiple abdominal cavity and retroperitoneal lymph node metastases. ERBB2 amplification and overexpression were identified in both case reports presented. The patients were treated with four cycles of oxaliplatin, capecitabine and trastuzumab. Computed tomography revealed the lymph node metastases decreased in size following treatment, and surgical resection was performed. The four cycles of oxaliplatin, capecitabine and trastuzumab were continued subsequent to surgical resection at the administered dose. No recurrence was observed for >1 year after surgery. Trastuzumab combined with oxaliplatin and capecitabine as a conversion therapy regime for ERBB2-overexpressing advanced gastric adenocarcinoma increased the likelihood of successful surgical resection, and prolonged progression-free survival.
10.3892/ol.2018.8942
Apatinib Combined With SOX Regimen in Conversion Treatment of Advanced Gastric Cancer: A Case Series and Literature Review.
Jiang Dingyi,Xu Yunyun,Chen Yunwang,Jiang Jiahong,Wang Mingxing,Yang Min,Chen Zheling,Yang Liu
Frontiers in pharmacology
Gastric cancer is a common digestive tract tumor and the second most prevalent cancer. The prognosis of advanced gastric cancer is poor. Conversion therapy can reduce tumor burden, downgrade tumor, and increase the possibility of complete resection, thus prolonging the survival time of patients with gastric cancer. In conversion therapy, chemotherapy and targeted therapy are the main methods of medical treatment, which can control tumor growth and recurrence. As an antiangiogenic targeted drug, apatinib is widely used in the third-line treatment of advanced gastric cancer. Recent studies have shown that it may be of great help in rapid reduction of tumor stage and improvement of prognosis in conversion therapy. This study reported three cases of gastric cancer complicated with multiple abdominal and retroperitoneal lymph node metastases. After receiving apatinib combined with SOX regimen for four cycles, computed tomography showed that the focus and lymph node metastasis were reduced after treatment, and primary tumors were resected. Postoperative pathology result showed that the patients got R0 resection. After radical surgery, the maintenance therapy including apatinib was given. The progression-free survival time was more than 10 months. Apatinib combined with SOX regimen as a conversion therapy for advanced gastric adenocarcinoma increases the possibility of successful surgical resection, which might prolong the survival time of patients.
10.3389/fphar.2020.01027
Long-term Results of Conversion Therapy for Initially Unresectable Gastric Cancer: Analysis of 122 Patients at the National Cancer Center in China.
Wang Tongbo,Wang Nianchang,Ren Hu,Zhou Hong,Zhou Aiping,Jin Jing,Chen Yingtai,Zhao Dongbing
Journal of Cancer
To assess the long-term survival and prognostic factors of conversion therapy in patients with initially unresectable gastric cancer. We conducted a retrospective study of clinicopathological and survival data of 122 consecutive patients who were diagnosed with initially unresectable gastric cancer and underwent the conversion surgery after systemic chemotherapy at the China National Cancer Center between May 2006 and May 2017. For all the 122 patients, the 3- and 5-year overall survival (OS) rates from the date of chemotherapy initiation were 61.0% and 52.0%, respectively, with a median OS of 63.6 months. During follow-up, the recurrence was observed in 49 (40.1%) patients who underwent conversion surgery. According to the multivariate COX regression analysis, receipt of postoperative adjuvant chemotherapy (POAC) was the only significant independent predictor of a favorable OS (HR 0.40; 95% CI 0.18-0.85, =0.017). Log-rank analysis showed that POAC group experienced a survival advantage in terms of PFS when compared with observation group (HR 0.53, 95%CI 0.31-0.92, =0.009). Conversion therapy may provide long-term survival for patients with initially unresectable gastric cancer. Postoperative adjuvant chemotherapy might be recommended for patients who underwent conversion therapy.
10.7150/jca.35527
CONVERSION THERAPY FOR GASTRIC CANCER: EXPANDING THE TREATMENT POSSIBILITIES.
Ramos Marcus Fernando Kodama Pertille,Pereira Marina Alessandra,Charruf Amir Zeide,Dias André Roncon,Castria Tiago Biachi de,Barchi Leandro Cardoso,Ribeiro-Júnior Ulysses,Zilberstein Bruno,Cecconello Ivan
Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery
BACKGROUND:Conversion therapy in gastric cancer (GC) is defined as the use of chemotherapy/radiotherapy followed by surgical resection with curative intent of a tumor that was prior considered unresectable or oncologically incurable. AIM:To evaluate the results of conversion therapy in the treatment of GC. METHODS:Retrospective analysis of all GC surgeries between 2009 and 2018. Patients who received any therapy before surgery were further identified to define the conversion group. RESULTS:Out of 1003 surgeries performed for GC, 113 cases underwent neoadjuvant treatment and 16 (1.6%) were considered as conversion therapy. The main indication for treatment was: T4b lesions (n=10), lymph node metastasis (n=4), peritoneal carcinomatosis and hepatic metastasis in one case each. The diagnosis was made by imaging in 14 cases (75%) and during surgical procedure in four (25%). The most commonly used chemotherapy regimens were XP and mFLOX. Major surgical complications occurred in four cases (25%) and one (6.3%) died. After an average follow-up of 20 months, 11 patients (68.7%) had recurrence and nine (56.3%) died. Prolonged recurrence-free survival over 40 months occurred in two cases. CONCLUSION:Conversion therapy may offer the possibility of prolonged survival for a group of GC patients initially considered beyond therapeutic possibility.
10.1590/0102-672020190001e1435
[A Case of Stage Ⅳ Gastric Cancer with Para-Aortic Lymph Node Metastasis, and Multiple Liver, Lung, and Bone Metastases Leading to Conversion Therapy].
Umemura Kotaro,Muroya Takahiro,Yoshida Eri,Umetsu Satoko,Sato Kentaro,Fujita Hiroaki,Hakamada Kenichi
Gan to kagaku ryoho. Cancer & chemotherapy
We report a case of unresectable gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases leading to conversion therapy. A 70s-year-old man visited previous doctor with epigastralgia. He was diagnosed as stage Ⅳ gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases by upper gastrointestinal endoscopy, contrast enhanced computer tomography(CT), and positron emission tomography(PET). After a regimen consisting of 6 courses of capecitabine plus cisplatin plus trastuzumab, para-aortic lymph node metastasis and liver, lung, and bone metastases were absent in CT and PET images. So, he visited our department for surgery treatment. We judged curative resection could be achieved for gastric cancer. Total gastrectomy, D2 and paraaortic lymphadenectomy, and cholecystectomy were performed. The histopathological examination of the resected specimen revealed the efficacy of chemotherapy was Grade 2b. The patient was discharge 14 days after the operation, and capecitabine plus trastuzumab was started as adjuvant chemotherapy, and the patient remains alive without recurrence 11 months after surgical treatment.
Surgical Outcome and Long-Term Survival of Conversion Surgery for Advanced Gastric Cancer.
Chen Guo-Ming,Yuan Shu-Qiang,Nie Run-Cong,Luo Tian-Qi,Jiang Kai-Ming,Liang Cheng-Cai,Li Yuan-Fang,Zhang De-Yao,Yu Jie-Hai,Hou Fan,Wang Yun,Chen Ying-Bo
Annals of surgical oncology
BACKGROUND:The present study aims to report the surgical outcome and long-term survival of conversion surgery and clarify its role in advanced gastric cancer. PATIENTS AND METHODS:A total of 95 primary advanced gastric adenocarcinoma patients who underwent systemic chemotherapy and conversion surgery were reviewed retrospectively. The survival of conversion surgery was analyzed by Cox regression and the Kaplan-Meier method. Surgical outcomes were analyzed according to the Clavien-Dindo classification. RESULTS:The median survival time (MST) of the 95 patients was 26.8 months, and the postoperative MST was 19.3 months. The MSTs of the patients in categories 1, 2, 3, and 4 were 28.8, 25.5, 43.6, and 11.3 months, respectively. The MSTs of the patients who underwent R0 resection (47 cases) and R1/2 resection (48 cases) were 49.3 months and 21.9 months, respectively. The MST of patients treated with total gastrectomy was shorter (21.9 months) than that of patients who underwent proximal (55.0 months) or distal (46.3 months) gastrectomy. Patients who received more than 6 cycles of induction chemotherapy had a longer MST than patients who received 3-5 cycles or 1-2 cycles (MST: 55.0 months versus 21.1 months versus 21.7 months). The incident postoperative complications and postoperative mortality rates were 10.5% and 1.1%, respectively. CONCLUSIONS:Advanced gastric cancer patients may obtain a survival benefit from conversion surgery, except category 4. Performing a sufficient number of cycles of induction chemotherapy (usually ≥ 6 cycles) is recommended. Surgical oncologists should perform R0 resection and avoid total gastrectomy.
10.1245/s10434-020-08559-7
[A Case of Type 4 Gastric Cancer with Peritoneal Dissemination Successfully Treated with Conversion Surgery after Intensive S-1 plus Oxaliplatin Chemotherapy].
Obana Ayato,Usui Shinsuke,Koyama Motoi,Koide Norimasa,Iwasaki Kenichi,Matsumura Tomonori,Sato Yoshinobu,Kitamura Kenta,Yoshida Ryuichi,Nomori Hiroaki,Suwa Tatsushi
Gan to kagaku ryoho. Cancer & chemotherapy
S-1 plus oxaliplatin(SOX)chemotherapy is now widely used for the treatment of unresectable gastric cancer but there are few case reports about conversion surgery following SOX. Hereby, we report a case of type 4 gastric cancer with peritoneal dissemination successfully treated with conversion surgery after intensive SOX chemotherapy. A 69-year-old female was diagnosed of type 4 gastric cancer by upper endoscopy(por1, HER2 negative)and peritoneal disseminations were identified on left diaphragm and mesentery under direct vision. After 11 courses of SOX chemotherapy, CT revealed that primary tumor markedly decreased in size. Therefore, staging laparoscopy was performed and peritoneal disseminated lesions disappeared. Peritoneal cytology also turned negative. Subsequently, total gastrectomy and splenectomy were performed. Histology revealed that tumor was categorized as por2, ypT2N3M0, ypStage ⅢA, and Grade 2 in histological evaluation criteria. SOX was continued as an adjuvant chemotherapy for another 6 months and the patients remain healthy without recurrence. Unresectable gastric cancer with peritoneal dissemination can be successfully treated with conversion surgery following SOX chemotherapy and staging laparoscopy was useful to evaluate peritoneal dissemination. When conversion surgery is indicated for gastric cancer with peritoneal dissemination, downstaging should be confirmed by staging laparoscopy.
Conversion surgery for stage IV gastric cancer with a complete pathological response to nivolumab: a case report.
Matsumoto Ryu,Arigami Takaaki,Matsushita Daisuke,Okubo Keishi,Tanaka Takako,Yanagita Shigehiro,Sasaki Ken,Noda Masahiro,Kita Yoshiaki,Mori Shinichiro,Kurahara Hiroshi,Ohtsuka Takao
World journal of surgical oncology
BACKGROUND:Patients with stage IV gastric cancer have a poor prognosis despite the recent development of multidisciplinary treatments that include chemotherapy. However, conversion surgery has emerged as a promising strategy to improve the prognosis in responders with unresectable gastric cancer after chemotherapy. Moreover, nivolumab is currently recommended as a third-line treatment in patients with unresectable advanced gastric cancer. However, there are few reports of conversion surgery after nivolumab in patients with stage IV gastric cancer. CASE PRESENTATION:A 68-year-old woman complaining of nausea was diagnosed with stage I gastric cancer (T2N0M0). Although we planned gastrectomy with lymphadenectomy, multiple liver metastases were detected during the surgery. After staging laparoscopy, we diagnosed this patient as having stage IV unresectable gastric cancer, and we administered chemotherapy and immunotherapy for 39 months (first-line regimen: 6 courses of S-1 plus oxaliplatin; second-line regimen: 6 courses of ramucirumab plus paclitaxel; and third-line regimen: 20 courses of nivolumab). Although the liver metastases completely disappeared after the second-line chemotherapy, lung metastases and a rapid enlargement of the primary tumor were confirmed. Consequently, the patient received nivolumab at a dose of 3 mg/kg intravenously every 2 weeks, then a dose of 240 mg/kg intravenously every 2 weeks from September 2018. After 20 courses of nivolumab, the primary tumor dramatically shrank and the lung metastases disappeared. The patient had a partial primary tumor response to nivolumab. Therefore, the patient underwent laparoscopic distal gastrectomy with D2 lymph node dissection. The macroscopic examination of the resected specimen showed an ulcer scar in the primary tumor site. The pathological examination demonstrated no residual tumors and no lymph node metastases, and the histological response of the primary tumor was categorized as grade 3. The postoperative course was uneventful, and the patient is receiving nivolumab to control potential liver and lung metastases. CONCLUSIONS:Conversion surgery might help control tumor progression in responders after chemotherapy and immunotherapy.
10.1186/s12957-020-01954-0
[Clinical significance and practice points of conversion therapy for gastric cancer with peritoneal metastasis].
Zhu Zhenggang
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
Gastric cancer with peritoneal dissemination is usually considered to be oncologically unresectable and is known to have a very poor prognosis. Despite recent advances in systemic chemotherapy, peritoneal dissemination due to advanced gastric cancer (AGC) still remains the most life-threatening type of metastasis and recurrence, which usually causes ascites accumulation, intestinal obstruction, or hydronephrosis, and then seriously impairs the quality of life. In general, the median survival time of these cases is reported to be just only 6-9 months. Recently, conversion therapy for gastric cancer with peritoneal dissemination has been highly concerned. It is defined as a conversion surgery aiming at an R0 resection after chemotherapy for both primary gastric cancer and distant metastatic cancerous foci including peritoneal dissemination, which were originally unresectable due to technical and/or oncological reasons. In numerous clinical practices, the results of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) have been reported to be more satisfactory in comparison with traditional systemic chemotherapy alone. Some clinical trials have demonstrated the clinical efficacy of intravenous and intraperitoneal administration of paclitaxel (PTX) combined with oral S-1 for peritoneal dissemination of gastric cancer with or without malignant ascites. Particularly, a longer period of survival can be expected when conversion R0 gastrectomy is successfully performed after observing significant responses of NIPS. Some clinical practice key points of conversion therapy for AGC patients with peritoneal dissemination are reviewed, including the importance of intraperitoneal and systemic synchronous chemotherapy, the reasonable choice of intraperitoneal chemotherapy drugs, the evaluation of primary gastric cancer and metastatic foci before and after conversion therapy, some special complications of NIPS, the indications of conversion surgery and the adjuvant therapy after conversion surgery, ect.
[Problems for the conversion therapy in advanced gastric cancer].
Wang P L,Xu H M
Zhonghua zhong liu za zhi [Chinese journal of oncology]
Patients with advanced gastric cancer have a poor prognosis, which remains the clinical concerned hot topic. The main previous treatments for advanced gastric cancer were adjuvant chemotherapy and palliative surgery, however, the application of conversion therapy has improved the survival in recent years. There are still many problems and challenges for conversion therapy because of its initial stage, such as the definition of advanced gastric cancer and conversion therapy, the selection of suitable population for conversion therapy, and the role of surgery in conversion therapy. Precision medicine will be applied to conversion therapy for advanced gastric cancer in the future, which would benefit more patients.
10.3760/cma.j.issn.0253-3766.2019.03.001
[Progress in conversion therapy for originally unresectable gastric cancer].
Chen Xinhua,Lin Zhousheng,Chen Yuehong,Luo Jun,Zhu Yu,Liu Hao,Li Guoxin,Yu Jiang
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
Conversion therapy is adopted to achieve radical cure for patients with originally unresectable but potentially resectable late stage gastric cancer, who obtain partial or complete remission after systemic chemotherapy, to acquire relatively longer postoperative survival and recurrence-free survival. Some of the previous researches on conversion therapy for originally unresectable gastric cancer suggest that high chemotherapy response rate, high pathological response rate and R0 resection rate are associated with favorable prognosis. And the efficacy of patients with lymphatic metastasis is better than that of those with peritoneal metastasis. The protocol of conversional chemotherapy varies and so does its efficacy according to different reports. Latest clinical researches indicate that initially unresectable gastric cancer gained higher remission rate and better chance of R0 operation and consequently prolonged survival from paclitaxel based triplet chemotherapy. However, not all originally unresectable gastric cancer can benefit from conversion therapy due to the high heterogeneity of its biological behavior. Regarding the enormous number of originally unresectable gastric cancer patients, it will be a research hot spot in the field of surgical oncology, on screening criteria to select cases suitable for conversion. Exploration on conversion therapy for gastric cancer is still at initial stage, and reports that have been published are mostly single-centered with limited sample, lacking of sufficient evidence on its feasibility, safety and efficacy. Expert consensus on conversion indication, case selection, chemotherapy regimen, efficacy assessment and resection range is absent. So it is in urgent need for higher level clinical evidence to support and guide this practice. Such goal can never be achieved without joint efforts of all parties to carry out clinical trial to modify the practice of conversion therapy for late stage gastric cancer, and determine the proper selection of suitable candidates for conversion therapy, eventually to offer optimal strategy for originally unresectable gastric cancer patients. Thus, this article focuses on reviewing research progress of conversion therapy for originally unresectable late stage gastric cancer.
[Clinical significance and efficacy of conversion surgery for patients with stage IV gastric cancer].
Zhu Zhenggang
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
Gastric cancer is the second most common malignancy and the one of the leading causes of cancer-related death in China. In particular, the survival rate of patients with stage IV or unresectable gastric cancer is very poor. Conversion therapy for stage IV gastric cancer has been the main subject with much attention recently. It is defined to achieve an R0 surgical resection after chemotherapy for originally unresectable cancer due to technical and/or oncological reasons. However, the optimal indications for conversion surgery are still controversial, and how to select the most appropriate candidates for conversion therapy remains to be clarified. A new biological category for stage IV gastric cancer proposed by K Yoshida from Gifu University has been tested out in some trials, from which stage IV gastric cancer can be divided into two different classifications based on the absence (category 1: potentially resectable metastasis and category 2: marginally resectable metastasis) or presence (category 3:incurable and unresectable metastasis and category 4: non-curable metastasis) of macroscopic peritoneal dissemination. The optimal indications for conversion therapy mainly include the patients with category 2, and partially for patients with categories 3 and 4. A surgery-oriented classification proposed by Peking University Cancer Hospital tried to classify the stage IV gastric cancer for conversion therapy. It would be classified as resectable and unresectable categories, depending on uhether R0 resection is available by preoperative evaluation. In this classification, unresectable cancer can be further classified as conversed, partly conversed and non-conversed types based on extent of cancer metastasis. The resection of primary and metastatic lesion in unscreened stage IV gastric cancer was not testified to improve survival. REGATTA trial has identified no significant difference in survival rate between the chemotherapy only and palliative gastrectomy with postoperative chemotherapy for stage IV gastric cancer with a single non-curable factor. With development of conversion therapy, a consensus has been reached that the patients with unresectable gastric cancer initially exhibiting one non-curative factor, if having clinical response to chemotherapy, may obtain a survival benefit from subsequent R0 radical gastrectomy. Several novel combined chemotherapy regimens occasionally allow for conversion of an initially unresectable gastric cancer to resectable cancer in clinical practice. Conversion surgery may result in long-term survival in selected patients who respond to chemotherapy. Several previous studies have evaluated the positive prognostic role of surgery after chemotherapy in stage IV gastric cancer patients with one non-curative factor, such as peritoneal metastasis, para-aortic lymph node metastasis or liver metastasis. Gastric cancer is a highly heterogeneous tumor in nature, consisting of varying aggressive biological characteristics. Oncologically stage IV gastric cancer is a systemic disease, and the complete response to any therapy is really very rare, so that conversion therapy is a great clinical challenging problem for gastric cancer patients. Due to the multi-pathway metastasis, perioperative systemic chemotherapy is the most important in conversion therapy for stage IV gastric cancer, and a radical surgical resection is the key to improve prognosis. A good local control does not necessarily lead to prolonged survival in patients with stage IV gastric cancer, in which other sites metastases often emerge even after successful local-regional cancer-oriented treatment. To date, most reports of conversion therapy for gastric cancer were from single-center or retrospective study. If more reliable evidences are to be obtained, more multi-center and prospective RCT studies must be carried out.
[Progress in conversion therapy for stage IV gastric cancer].
Liang H
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
Gastric cancer is one of the most common malignancy in China. Most of the patients of gastric cancer treated clinically are in advanced stage. In the past years, with the progress of anti-cancer drug therapy, after the comprehensive treatment based on drugs therapy of inoperative stage IV gastric cancer, some cases can reduce the tumor stage and get the opportunity of radical operation. Some of the patients who underwent surgical treatment can get the chance of long-term survival. The results of REGATTA trial confirmed that palliative surgery plus chemotherapy could not improve the long-term survival of patients with stage IV gastric cancer. Neoadjuvant intraperitoneal plus intravenous chemotherapy can reduce the tumor stage of some cases of stage IV gastric cancer with peritoneal metastasis and receive surgical treatment, so as to gain the chance of long-term survival. Regimen of intraperitoneal hyperthermia chemotherapy combined with PHOENIX trial is expected to improve the conversion operation rate of gastric cancer with peritoneal metastasis. Paclitaxel-based three-drug chemotherapy can reduce the tumor stage of some inoperable advanced gastric cancer and obtain the opportunity of radical operation, improving the disease-free survival rate and overall survival rate of patients, thus has become the cornerstone of conversion therapy for stage IV gastric cancer. Antiangiogenic targeted drug apatinib combined with paclitaxel is safe and reliable, and can be used as an alternative for the conversion therapy of stage IV gastric cancer, which provides a new idea for cytotoxic drugs combined with targeted drugs. In the era of immunotherapy, the combined application and first-line application of immunosuppressive drugs has become a clinical consensus. For advanced Her-2 positive esophagogastric junction adenocarcinoma cases, the successful exploration of the four-drug combination of chemotherapy+ anti-Her-2 targeted drugs+ anti-PD1 monoclonal antibody combined with the first-line therapy has opened up a new era of transformational therapy for stage IV gastric cancer. Gastric cancer is a malignant tumor with high heterogeneity, the classification of stage IV gastric cancer represented by Yoshida classification is based on imaging, and a more reasonable classification method should be developed in combination with gene detection in the future. Based on this, an individualized and accurate conversion therapy plan is formulated, so as to effectively improve the long-term survival of patients with stage IV gastric cancer.
10.3760/cma.j.cn.441530-20201215-00661